Congenital Midline Cervical Cleft: First Report and Genetic Analysis of Two Related Patients

Ann Otol Rhinol Laryngol. 2020 Jul;129(7):653-656. doi: 10.1177/0003489420906180. Epub 2020 Feb 6.


Objectives: Congenital midline cervical cleft (CMCC) is a rare congenital anterior neck anatomical anomaly. We present the case of two related patients (grandchild and maternal grandmother) who were both born with a congenital midline cervical cleft along with genetic analysis.

Methods: Clinical examination of both patients and surgical excision of the grandchild was performed. Genetic analysis with exome sequencing (ES) was conducted for both patients.

Results: Genetic analysis with exome sequencing (ES) revealed apparently novel single nucleotide variants in 66 genes present in both proband and grandmother. Five of these variants are predicted to cause frameshifting in the coding region of the respective genes and truncated proteins (OVGP1, TYW1B, ZAN, SSPO, FOLR3). Two of these genes (TYW1B and SSPO) have homozygous indel mutations in both patients.

Conclusions: To our knowledge, this is the first case of two related patients with a congenital midline cervical cleft. The results of our genetic analysis reveal potential relevance to CMCC development.

Keywords: congenital midline cervical cleft; exome sequencing; head and neck surgery; neck mass; pediatric branchial cleft abnormalities.

Publication types

  • Case Reports

MeSH terms

  • Branchial Region / abnormalities*
  • Branchial Region / surgery
  • Carrier Proteins / genetics*
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / surgery
  • Exome Sequencing
  • Female
  • Frameshift Mutation
  • Glycoproteins / genetics*
  • Grandparents
  • Humans
  • INDEL Mutation
  • Infant, Newborn
  • Male
  • Middle Aged
  • Mixed Function Oxygenases / genetics
  • Neck / abnormalities*
  • Neck / surgery
  • Pharyngeal Diseases / genetics*
  • Pharyngeal Diseases / surgery
  • Polymorphism, Single Nucleotide


  • Carrier Proteins
  • Cell Adhesion Molecules, Neuronal
  • FOLR3 protein, human
  • Glycoproteins
  • OVGP1 protein, human
  • SCO-spondin
  • Mixed Function Oxygenases

Supplementary concepts

  • Branchial Cleft Anomalies